Engineering terminal disulfide bonds into DNA

This protocol presents a simple and general means of modifying nucleic acids with disulfide cross-links. These cross-links serve as powerful tools to probe the structure, dynamics, thermodynamics, folding, and function of DNA and RNA, much in the way that cystine cross-links have been used to study proteins. The chemistry described has been used to synthesize disulfide-cross-linked hairpins and duplexes, higher-order structures such as triplexes, non-ground-state conformations, and tRNAs. since the cross-links form quantitatively by mild air oxidation and do not purturb either secondary or tertiary structure, this modification should prove quite useful for the study of nucleic acids.